Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Physiology, Hanlin College, Nanjing University of Chinese Medicine, Taizhou 225300, China.
Department of Endocrinology, Pukou Branch of Jiangsu People's Hospital, Nanjing 211808, China.
Mech Ageing Dev. 2021 Mar;194:111427. doi: 10.1016/j.mad.2020.111427. Epub 2020 Dec 28.
Type 2 diabetes mellitus (T2DM) and osteoporosis are two major healthcare problems worldwide. T2DM is considered to be a risk factor for osteoporosis. Interestingly, several epidemiological studies suggest that bone abnormalities associated with diabetes may differ, at least in part, from those associated with senile or post-menopausal osteoporosis. The growing prevalence that patients with T2DM simultaneously suffer from osteoporosis, puts forward the importance to discuss the relationship between both diseases, as well as to investigate correlative agents to treat them. Emerging evidences demonstrate that neuropeptide galanin is involved in the pathogenesis of T2DM and osteoporosis. Galanin via activation of central GALR2 increases insulin sensitivity as well as bone density and mass in animal models. The disorder of galanin function plays major role in development of both diseases. Importantly, galanin signaling is indispensable for ΔFosB, an AP1 antagonist, to play the bone mass-accruing effects in the ventral hypothalamic neurons of diabetic models. This review summarizes our and other recent studies to provide a new insight into the multivariate relationship among galanin, T2DM and osteoporosis, highlighting the beneficial effect of galanin on the comorbid state of both diseases. These may help us better understanding the pathogenesis of osteoporosis and T2DM and provide useful clues for further inquiry if elevated galanin level may be taken as a biomarker for both conjoint diseases, and GALR2 agonist may be taken as a novel therapeutic strategy to treat both diseases concurrently.
2 型糖尿病（T2DM）和骨质疏松症是全球两个主要的医疗保健问题。T2DM 被认为是骨质疏松症的一个危险因素。有趣的是，几项流行病学研究表明，与糖尿病相关的骨骼异常至少在一定程度上与与衰老或绝经后骨质疏松症相关的骨骼异常不同。越来越多的 T2DM 患者同时患有骨质疏松症，这就提出了讨论这两种疾病之间关系的重要性，以及研究相关的治疗药物。新出现的证据表明，神经肽甘丙肽参与了 T2DM 和骨质疏松症的发病机制。甘丙肽通过激活中枢 GALR2 增加了动物模型中的胰岛素敏感性以及骨密度和骨量。甘丙肽功能障碍在这两种疾病的发展中起着重要作用。重要的是，甘丙肽信号对于ΔFosB（AP1 拮抗剂）在糖尿病模型的腹侧下丘脑神经元中发挥增加骨量的作用是必不可少的。本综述总结了我们和其他最近的研究，为甘丙肽、T2DM 和骨质疏松症之间的多变量关系提供了新的见解，强调了甘丙肽对这两种疾病并发状态的有益作用。这些可能有助于我们更好地理解骨质疏松症和 T2DM 的发病机制，如果甘丙肽水平升高可以作为这两种疾病的生物标志物，那么 GALR2 激动剂是否可以作为同时治疗这两种疾病的新的治疗策略，为进一步的研究提供有用的线索。
